Tumor Targeting Peptides

The selective targeting of tumor is a promising strategy to detect and/or treat cancer. We are interested in the design of synthetic peptide vectors to specifically deliver biomolecules or other active molecules (markers, drugs) into cells that overexpress a protein receptor on their surface.

We develop macromolecular compounds comprising “RGD” ligands that target α_Vβ₃ integrin overexpressed in the tumor microenvironment. We have designed RGD-containing vectors that exhibit biological properties for:
   - Capture of tumor cells (J. Mat. Chem. B 2017)
   - Tumor imaging, optical guided surgery of tumors (Cancer Lett. 2013)
   - Targeted drug delivery (Mol. Ther. 2017 ; Chem. Eur. J. 2020)

We have shown the importance of macromolecular architecture in tems of multimeric presentation of ligands and linker lenghts (J. Am. Chem. Soc. 2004 ; ChemBioChem 2016).

All compounds are prepared by using peptide synthesis and biomolecular assemblies via orthogonal chemoselective ligations (more info). Several projets are in progress to deliver “drugs” for instance for photodynamic therapy.

Recent collaborations:

• X. Le Guevel, V. Josserand, V. Frachet, J. L. Coll (Institute for Advance Biosciences, Grenoble)
• A. Favier (Ingénierie des Matériaux Polymères, Lyon)
• Z.-H. Jin (National Institute of Radiological Sciences, Chiba, Japan)
• Y. Roupioz (SyMMES, CEA, Grenoble)
• O. Sénèque (LCBM, CEA, Grenoble)
• R. Tripier (Laboratoire Chimie Electrochimie Moléculaires et Chimie Analytique, Brest)

In Parallel, we aim to design small monoclonal antibody (mAb) mimics by using an entire synthetic approach. MAbs have emerged as a promising class of pharmaceuticals for the treatment of many human diseases including cancer. However, their high cost of production, large size and polymorphism are major limiting factors. In this context, we developed antigenic surfaces displaying the CD20 epitope that is specifically recognized by rituximab, mAb indicated for the treatment of patients with non-Hodgkin's lymphoma (Anal. Chem. 2020). These surfaces are exploited for the screening of mAb mimics by using the SPR (surface plasmon resonance) technique (more info). To date, we identified short fragments from the Fab of rituximab that exhibit high affinity for the CD20 epitope (Anal. Chem. 2021).

Recent collaborations:

• E. Peyrin (Département de Chimie Moléculaire, Grenoble)
• V. Frachet, J. L. Coll (Institute for Advance Biosciences, Grenoble)